We will investigate the feasibility of flow cytometric analysis of DNA, RNA, protein, nucleolar antigen and cell volume to identify the presence of tumor cells in clinical material. The relative sensitivity and specificity of automated cytology to detect tumor cells will be compared to standard light and electronmicroscopic evaluations. Furthermore, flow cytometric parameters will be sought that reflect the degree of tumor differentiaton and grading, in order to provide a clinically useful classification in the areas of lung, bladder and prostate carcinomas and of malignant lymphomas. We will assess whether such cellular probes vary with the site of neoplastic disease (TNM) and thus provide quantitative cellular features determining the sites of metastatic spread. For human breast cancer, we will develop concurrent DNA/estrogen receptor (ER) flow cytometry to permit measurements of ER quantity on a per-tumor-cell basis and with regard to cell cycle position. The generated information will facilitate a more objective and quantitative means of cancer diagnosis and prognosis.